FADD

In the first installment of this two-part blog post titled "Apoptosis and Necroptosis: Important factors to identify both types of programmed cell death", the mechanisms by which cell death occurs and ways to identify these pathways were discussed. In this next segment, we focus on the molecular factors regulating the choice between programmed cell death and survival signaling.

Different types of cell death have classically been identified by discrete morphological changes. The hallmarks of apoptosis include cell shrinkage, nuclear fragmentation and membrane blebbing whereas necroptosis is characterized by cell swelling and plasma membrane breakdown. While these two forms of cell death are clearly distinct, substantial crosstalk occurs between them.  Accordingly, it is becoming increasingly important to understand how these processes differ and to understand ways to differentiate them in cellular populations. 

FAS-associated death domain protein (FADD) is a 23 kDa adaptor protein involved in initiating apoptosis. FADD is best known for its involvement in extrinsic/death receptor-mediated apoptosis, but it is also involved in initiating necroptosis with serine/threonine kinases RIPK1 and RIPK3 (1). FADD binds to receptors of the tumor necrosis factor (TNF) superfamily through its C-terminal death domain (DD). During extrinsic apoptosis, binding of the Fas-ligand causes trimerization of the Fas-receptor which then binds to FADD via the DD domain.

Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. Among the subclass of initiator caspases that include subtypes -2, -8 and -9, caspase 9 is expressed in a variety of human tissues.